gms | German Medical Science

Background/research question: Background. The term “cannabinoid” encompasses broad spectrum of pharmacologically active products, natural and synthetic. In the research-dense area of cannabinoid-based products (CBP), it is unclear whether published systematic reviews (SR) provide physicians with sufficient clarity to prescribe properly each medicinal cannabinoid product.

Objective. To investigate features, quality and clinical relevance of published SR (with or without meta-analysis, MA) of clinical studies of CBP in multiple sclerosis (MS) related symptoms

Methods: SR published from January 1, 2011 to February 2, 2021 were identified during structured searches in PubMed using search terms and synonyms for relevant chemical entities and preparations, MS, as well as manual search in reference lists of overviews of SR. The risk-of-bias, reporting and methodological quality was evaluated by two reviewers using ROBIS [1].

Results: The search identified 8 SR, 5 with MA, 4 of which reported MA for more than one indication. The number of RCTs included in the SR ranged from 12 to 30. Where reported, the total number of patients was 2,280 to 3,161, study duration varied from 3 days to 3 years. All SR and most MA grouped CBP together without consideration of their differential attributes such as active substance(s), concentration/strength, dosage, forms, route of administration, or treatment duration. Those attributes were sufficiently reported only in 2 SR. Patient populations and outcome measures were also inhomogeneous. Separate results for specific cannabinoid formulations were rarely provided. Only three SR reported formal risk-of-bias assessment. According to ROBIS, 3 of 8 SR had “high” and 1 SR “unclear” overall risk-of-bias. The domain “Synthesis & findings” was rated “unclear” for 5 and “high” for 1 SR. Among the 5 SR with MA, 3 reported benefit of CBP comparing to placebo for reducing spasticity, 1 reported no benefit, and 1 was equivocal due to low certainty of evidence. None of SR reported results separately for specific CBP, dosage, forms or routes of administration.

Conclusion: The therapeutic effect of individual CBP was not clearly reflected in the published SR of clinical studies of CBP in MS related symptoms, which makes their clinical interpretation difficult. To truly inform evidence-based medical practice, whenever possible, SR and MA should aim to present results separately by product using the differential attributes in a specific and well-defined patient population.

Competing interests: Authors are employees of Almirall. There are no relevant conflicts of interests related to this work.